The coordinated spread of electrical slow waves is the underlying mechanism that produces gastrointestinal (GI) motility. The frequency of slow waves regulates motility processes by controlling the number of contractions and by influencing their strength and duration. The frequency, amplitude and duration of slow waves is regulated by the refractory period which follows each event. The slow wave refractory period is sufficiently long in duration to affect normal gastric activity at physiologic pacing frequencies. The refractory period may also play a role in the aberrant waveforms seen in gastric dysrhythmias. Refractoriness may be a result of: i) channels that increase membrane conductance and carry ionic currents during the refractory period; ii) channels that are inactivated during the refractory period and require time to reset. These channels would not be available for regenerative processes. iii) channels that are inactive at resting membrane potentials but active upon depolarization. These channels may be dependent upon second messengers, such as intracellular calcium. Experiments will be conducted to test each of these hypotheses. Once ionic mechanisms have been identified, it will be possible to determine the effects of excitatory and inhibitory transmitters (both of which can increase slow wave frequency) by their effect on channels responsible for the refractory state. It will also be possible to quantify differences in different regions of smooth muscle tissue to determine why some regions of tissue tend to generate slow waves at higher frequencies, and therefore serve as pacemaker sites. Methods to address thee issues include intracellular recordings, patch clamp techniques, and fluorescence measurements using calcium-sensitive dyes. These experiments should provide an understanding of the basic mechanisms that control rhythmicity and the patterns of contractions responsible for gastric motility.